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Poly[ N ‐(2‐hydroxypropyl)methacrylamide] prodrug for metaxalone via a chloroacetyl chloride linker: Synthesis and controlled release evaluation
Author(s) -
Zhang Juan,
Liu YiFeng,
Liu LinXue,
Zhang YaZhou,
Qiao ChangAn,
Zhou YongZhu
Publication year - 2012
Publication title -
journal of applied polymer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.575
H-Index - 166
eISSN - 1097-4628
pISSN - 0021-8995
DOI - 10.1002/app.36390
Subject(s) - methacrylamide , prodrug , hydrolysis , conjugate , chemistry , drug delivery , chloroacetyl chloride , copolymer , polymer chemistry , combinatorial chemistry , organic chemistry , polymer , chloride , biochemistry , acrylamide , mathematical analysis , mathematics
Poly[ N ‐(2‐hydroxypropyl)methacrylamide] (PHPMA) and its drug conjugates are some of the most intensively investigated drug‐delivery systems. Metaxalone (Met) was covalently linked to PHPMA via a spacer, and the procedure of the chemical modification for PHPMA was conducted by a two‐step protocol: (1) synthesis of PHPMA with different molecular weights and (2) synthesis of PHPMA–Met. The Met content in the conjugate could reach 18%. The controlled drug‐release studies were performed in buffer solutions with pH values equal to 1.1, 7.4, and 10.0. The results demonstrate that the rate of hydrolysis for PHPMA–Met was the slowest at pH 1.1, and a greater amount of Met was detected releasing from prodrug matrices in the presence of enzyme in a buffer solution at pH 8.0. It was also found that the novel prodrug effectively improved Met's pharmacokinetics and, furthermore, markedly increased its half‐life period. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012